Cervical Cancer Screening: The Key to Prevention

Padma Ravichandran, Danielle Pavliv and Brandel France de Bravo, MPH

June 2012

Cervical Cancer and the Human Papilloma Virus (HPV)

The cervix is the lowest part of a woman’s uterus, connecting the uterus to the vagina. During childbirth, the baby leaves the uterus where he or she has been growing and squeezes past the cervix to pass through the vagina or birth canal.

Cancer of the cervix (cervical cancer) is the third most common form of cancer among women worldwide after breast cancer. In the initial stages of the disease, there often aren’t any symptoms, and the symptoms that do appear can be mistaken for other health conditions. These symptoms include: continuous vaginal discharge, vaginal bleeding between periods or after intercourse, vaginal bleeding after menopause, or heavier and longer periods. In the later stages of the cancer, a woman might have any of the following symptoms: weight loss, loss of appetite, fatigue, pelvic pain, back pain, leg pain, one swollen leg, heavy vaginal bleeding, urine or feces leaking from the vagina, or bone fractures.[1]

Almost all cervical cancer is caused by infection with the Human Papilloma Virus (HPV).[2] It is very easy to get infected with HPV because it spreads by skin to skin contact of the genitals or genital contact with mucous membranes (such as in the vagina, anus, or mouth). At least half of all sexually active men and women have been infected with HPV at some point in their lives.[3]

Although about 95 % of women diagnosed with cervical cancer show evidence of HPV infection, the vast majority of women who have been infected with HPV do not develop cervical cancer.[4] There are at least 40 strains of sexually transmitted HPV that affect the genitals, but HPV strains 16 and 18 cause approximately 70% of all cases of cervical cancer.[5]

Women exposed to HPV in their twenties or earlier are able to clear the virus more quickly than women exposed later in life. As women get older, it takes longer for their body to get rid of the infection, which increases their chance of developing cervical cancer.[6]

Our bodies clear most HPV infections within 1-2 years, but the longer an infection lingers, especially strains 16 and 18, the more likely it will progress to pre-cancer. HPV can cause the cells of the cervix to grow abnormally, and abnormal cells can sometimes become pre-cancerous.[7]

Abnormal or precancerous cells often go away on their own (becoming normal cells again) without treatment. Since it is impossible to predict whether treatment is needed or not, the Pap smear test screens for abnormal and precancerous cells on the cervix.

About 6% of all Pap smears find abnormal cells or pre-cancers requiring follow-up, and those are surgically removed so that they won’t become cancerous.[8]

Cancers take years to develop, but cervical cancer tends to develop earlier in life than other cancers because HPV exposure often happens in late adolescence or early adulthood when people are most likely to have more than one sexual partner. Doctors have diagnosed precancerous growths or lesions on the cervix in women as young as 25 years old, but cervical cancer is usually diagnosed in women between the ages of 35-55.

Although HPV is the main cause of cervical cancer, smoking, having multiple births, and long-term use of oral contraceptives each increase the risk.[9]

Screening Tests

In order to identify any precancerous or cancerous cells before they become life-threatening, doctors encourage women to get routine Papanicolaou (Pap Smear) tests. Depending on a woman’s age, the doctor may also recommend one of the HPV tests.[10]

Pap Smear

The Pap smear, also known as cytology screening, is done in a doctor’s office, along with a pelvic exam. The gynecologist will take a sample of the cervical mucus and cervical cells and send them to the lab for testing. There, they look for abnormal cells or precancerous cells that might eventually become cancerous.[11] The Pap smear has long been used to screen for cervical cancer. In countries where this screening test is widely available, the number of cases of cervical cancer and the number of deaths from the disease have dropped dramatically.[12] In the United States, there has been a 70% reduction in cervical cancer incidence and mortality since the introduction of Pap smears.[13]

Researchers have found that women who have never gotten a Pap smear are three to ten times more likely to develop invasive cervical cancer than women who get routine screening.[14] Though precancerous cells can sometimes progress to cancer in as little as a year, that is rare and expert guidelines do not recommend annual screening for most women.

How often should you get a Pap Smear?

Not everyone agrees on when a woman should first get screened for cervical cancer and how often she should get screened. Recommendations given by different organizations over the years have varied. The one thing everyone seems to agree on is that there should be a minimum age and that beginning to screen too early is ineffective and even harmful. Young women often have abnormal cells on the cervix that the body can get rid of naturally. Positive Pap smear results, indicating the presence of abnormal cells, may lead a woman to undergo unnecessary treatment procedures that could cause emotional distress and physical discomfort.[15] Also, as a result of unnecessary treatment, these young women are more likely to have premature babies and babies with low-birth-weight.[16]

In 2012, the United States Preventive Services Task Force and a coalition consisting of the American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology released guidelines for screening for cervical cancer. [17][18] While the two sets of guidelines were created separately, they are consistent with one another. The chart below lists the newest recommendations for women as developed by these agencies and organizations. Cervical cancer screening guidelines are different if you have HIV/AIDS or have a suppressed immune system, if your mother took DES (diethylstilbestrol) when she was pregnant with you, or if you have already been told you have, or have been treated for, abnormal cells, precancerous cells, or cervical cancer.

Age group USPSTF and ACS/ASCCP/ASCP guidelines
Under 21 years Should not be screened regardless of the age of sexual initiation or other risk factors
21-29 years Recommends screening with cytology alone every 3 years
30-65 years Screening with cytology and HPV testing (known as “co-testing”) every 5 years is preferred, but cytology screening alone every 3 years is acceptable
Older than 65 years Women who have had negative screenings for the past 20 years and are not otherwise at high risk for cervical cancer should not be screened.*ACS/ASCCP/ASCP adds that screening should not be resumed for any reason, even if a woman reports a new sexual partner
After hysterectomy(surgery to remove the uterus) Women of any age who have had a hysterectomy   with removal of the cervix and who do not have a history of a high-grade precancerous lesion or cervical cancer should not be screened.

HPV Tests

The HPV test is done on the same sample of cervical cells and cervical mucus. When checking for abnormal or cancerous cells, the laboratory specialist can also check the cells for the HPV virus. There are two types of high risk HPV tests:  the Digene hc2 High Risk HPV Test and Cervista HPV HR test. The company that makes the Cervista HPV HR test recently developed a test that specifically looks for strains 16 and 18.

The Digene hc2 High Risk HPV Test has been around for some years and checks for thirteen high risk strains of HPV, including HPV 16 and 18. While this test can determine if a woman is infected with a high risk strain, it is not that effective at identifying which high risk HPV strain she has.[19]The second high risk HPV test, Cervista HPV HR is similar to the Digene hc2 High Risk HPV Test in that it screens for high risk strains of HPV. The difference between these two tests is that the Cervista HPV HR screens for fourteen strains compared to the thirteen that the Digene hc2 High Risk HPV Test screens for. Both tests are approved by the Food and Drug Administration (FDA) to screen for high risk strains of HPV in women over the age of 30. This means that the test is not approved for women under 30, even if they have an abnormal Pap smear. Women under 30 who are given this HPV test have a good chance of getting a false positive reading[20] (the test falsely says that she has HPV), which is why it is not approved for this age group.

The newest test, Cervista HPV 16/18, is a test that checks specifically for HPV 16 and 18, which are the strains responsible for most cases of cervical cancer. The drawback to this particular test is that it must be administered together with the Cervista HPV HR test.   Similar to the high risk HPV tests, the Cervista HPV 16/18 can only be administered on women above the age of 30.[21]

The HPV tests are helpful to physicians whose patients over 30 have had Pap smears with abnormal or precancerous cells. A woman who has precancerous cells and a positive HPV test is more likely to develop cervical cancer. The HPV test confirms that the woman has strains of HPV that could cause cancer.[22] The doctors are more likely to recommend immediate follow-up or treatment for these women than women with precancerous cells and no evidence of a high risk strain of HPV.

Women under 30 must rely exclusively on Pap smears once every three years for detecting and keeping a watchful eye on changes in cervical cells. The HPV test is of no use for women in this age group, because even if they are infected with one or more types of HPV most will be able to rid themselves of infection relatively quickly. If young women with abnormal Pap smears were given the HPV test, they would be likely to receive unnecessary treatment which could harm their reproductive system.[23]

The Bottom Line:

Cervical cancer screening is simple, low-cost, and saves lives. Women should start getting Pap smears at 3-year intervals at age 21, and women over 30 whose Pap smear showed abnormal cells or pre-cancers may want to also get one of the HPV tests.

References


[1]U.S. National Library of Medicine and National Institutes of Health. (2008). Cervical Cancer. Retrieved 18 February 2010, from the MedLine Plus Web Site:     http://www.nlm.nih.gov/medlineplus/ency/article/000893.htm

[2] zur Hausen, H. (2009). Papillomaviruses in the causation of human cancers-a brief historical account.  Virology, (384). 260-265.

[3] Center for Disease Control and Prevention. (2009). Genital HPV Infection-CDC Fact Sheet. Retrieved 9 February 2010 from the Center for Disease Control and Prevention Web Site: http://www.cdc.gov/STD/HPV/STDFact-HPV.htm

[4] National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages

[5] National Cancer Institute. (2008). Human papillomaviruses and cancer: Questions and answers. Retrieved 3 February 2010, from the National Cancer Institute Web Site:  http://www.cancer.gov/cancertopics/factsheet/Risk/HPV

[6] Schiffman, M., Castle, P.E., Jeronimo, J., Rodriguez, A.C. & Wacholder, S. (2007). Human papillomavirus and cervical cancer. Lancet (370). 890-907.

[7] Schiffman, M., Castle, P.E., Jeronimo, J., Rodriguez, A.C. & Wacholder, S. (2007). Human papillomavirus and cervical cancer. Lancet (370). 890-907.

[8] National Cancer Insitute. Pap Test Fact Sheet. http://www.cancer.gov/cancertopics/factsheet/Detection/Pap-test . Retrieved 17 February, 2010.

[9] Schiffman, M., Castle, P.E., Jeronimo, J., Rodriguez, A.C. & Wacholder, S. (2007). Human papillomavirus and cervical cancer. Lancet (370). 890-907.

[10] Center for Disease Control and Prevention. (2009). Cervical cancer screening. Retrieved 1 Feb 2010  from the Center for Diseases Control and Prevention Web Site:    http://www.cdc.gov/cancer/cervical/basic_info/screening.htm

[11] Center for Disease Control and Prevention. (2009). Cervical cancer screening. Retrieved 1 Feb 2010, from the Center for Diseases Control and Prevention Web Site:    http://www.cdc.gov/cancer/cervical/basic_info/screening.htm

[12] National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages

[13] Baseman, J.G., Kulasingam, S.L., Harris, T.G., Hughes, J.P., Kivat, N.B., Mao, C., Koutsky, L.A. (2008). Evaluation of primary cervical cancer screening with an oncogenic human papillomavirus DNA test and cervical cytologic findings among women who attended family planning clinics in the United States. American Journal of Obstetrics and Gynecology(26). E1-E8.

[14] National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages

[15] National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages

[16] Samya, G.F. (2009). Cervical cancer screening-New guidelines and the balance between benefits and harms. New England Journal of Medicine (361). 2503-2505.

[17] Saslow D, Solomon D, Lawson HW, Killackey M, Kulasingam SL, Cain J,…Myers E. (2012). American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. American Journal of Clinical Pathology. (137).516-542.

[18] Whitlock EP, Vesco KK, Eder M, Lin JS, Senger CA, Burda BU. (2011). U.S. Preventive Services Task Force. Liquid -based cytology and human papillomavirus testing to screen for cervical cancer. Retrieved 4 June 2012 at: http://www.uspreventiveservicestaskforce.org/uspstf11/cervcancer/cervcancerupd.htm

[19] National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site:                 http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages

[20] Food and Drug Administration. (2003). Summary of safety and effectiveness data: Digene hybrid capture 2 high-risk HPV DNA test. Retrieved 8 Feb 2010, from the Food and Drug Administration Web Site: http://www.accessdata.fda.gov/cdrh_docs/pdf/P890064S009b.pdf

[21] Food and Drug Administration. (2009). Summary of safety and effectiveness data: Cervista HPV 16/18. Retrieved 8 February 2010, from the Food and Drug Administration Web Site:               http://www.accessdata.fda.gov/cdrh_docs/pdf8/P080015b.pdf

[22] Naucler, p. et al. (2009). Efficacy of HPV DNA testing with cytology triage and/or repeat HPV DNA  testing in primary cervical cancer screening. Journal of the National Cancer Institute (101). 88-99.

[23] National Cancer Institute. (2009). PDQ cancer information summaries: Cervical cancer. Retrieved 2 February 2010, from the National Cancer Institute Web Site: http://www.cancer.gov/cancertopics/pdq/screening/cervical/healthprofessional/allpages

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